Schering (German Pat. No. 3,129,906) by Gries, Rosenberg, and Weinstien teaches the incorporation of paramagnetic metals into diethylene triamine pentaacetic acid (DTPA) forming chelates useful as a contrast agent in magnetic resonance imaging. The contrast agent DTPA-(GdIII) as taught by Schering is insoluble in water and requires the addition of cations "C+" (amines such as glucamine, N-methylglucamine, etc.) as shown below: The charge balance of the Schering DTPA-Gd(III) ion is:
______________________________________ Schering DTPA-Gd(III) Charge Balance ______________________________________ C+ C+ DTPA Gd +1 +1 -5 +3 = 0 ______________________________________
The resulting contrast agent has three ion particles in solution for each paramagnetic atom (a particle to PM ratio of 3:1). A paramagnetic metal with a valence of two, such as Mn, would require an additional glucamine ion:
______________________________________ Schering DTPA-Mn(II) Charge Balance ______________________________________ C+ C+ C+ DTPA Mn +1 + +1 +1 -5 +3 = 0 ______________________________________
raising the PM to particle ratio to 4:1.
These contrast agents raise the in vivo ion concentration and disturb the local osmolarity balance. The osmolarity is normally regulated at about 300 milliosmols per liter. Increasing the osmolarity with injected ions, causes water to collect within the unbalance region which dilutes the ion concentration.